PF-07225570 Alone or in Combination With an Anti-PD-1 Antibody in Recurrent Non-muscle Invasive Bladder Cancer (NMIBC)

Sponsor
Pfizer (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05259397
Collaborator
(none)
130
12
4
72.7
10.8
0.1

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of PF-07225570 alone or in combination with an anti-PD-1 antibody in participants with recurrent non-muscle invasive bladder cancer. This study consists of 2 parts, single agent dose escalation (Part 1A), dose finding of PF-07225570 in combination with anti-PD-1 antibody (Part 1B) and dose expansion (Part 2).

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
130 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND EXPANSION STUDY OF PF-07225570 EITHER ALONE OR IN COMBINATION WITH AN ANTI-PD-1 ANTIBODY, IN PARTICIPANTS WITH RECURRENT NON-MUSCLE INVASIVE BLADDER CANCER
Actual Study Start Date :
Mar 24, 2022
Anticipated Primary Completion Date :
Mar 15, 2027
Anticipated Study Completion Date :
Apr 13, 2028

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1A PF-07225570 monotherapy

Intravesical (IVe) Single Agent Dose Escalation

Drug: PF-07225570
PF-07225570 given IVe in a 28-day cycle (as induction and maintenance regimen). Multiple dose levels will be evaluated.

Experimental: Part 1B PF-07225570 and sasanlimab

PF-07225570 IVe and sasanlimab Subcutaneous (SQ) Combination Dose Escalation

Drug: PF-07225570
PF-07225570 given IVe in a 28-day cycle (as induction and maintenance regimen). Multiple dose levels will be evaluated.

Drug: sasanlimab
Sasanlimab will be administered SQ on day 1 of each 28 day cycle.
Other Names:
  • anti-PD-1 (programmed cell death protein-1) antibody
  • Experimental: Part 2A PF-07225570 monotherapy

    IVe Single Agent Dose Expansion

    Drug: PF-07225570
    PF-07225570 given IVe in a 28-day cycle (as induction and maintenance regimen). Multiple dose levels will be evaluated.

    Experimental: Part 2B PF-07225570 and sasanlimab

    PF-07225570 IVe and sasanlimab SQ Combination Dose Expansion

    Drug: PF-07225570
    PF-07225570 given IVe in a 28-day cycle (as induction and maintenance regimen). Multiple dose levels will be evaluated.

    Drug: sasanlimab
    Sasanlimab will be administered SQ on day 1 of each 28 day cycle.
    Other Names:
  • anti-PD-1 (programmed cell death protein-1) antibody
  • Outcome Measures

    Primary Outcome Measures

    1. Number of participants with Dose limiting toxicities [Baseline up to 28 days]

    2. Number of Participants with Adverse Events (AEs) according to Severity [Baseline up to approximately 24 months]

    3. Number of Participants with AEs according to Seriousness [Baseline up to approximately 24 months]

    4. Number of Participants with AEs according to Relationship [Baseline up to approximately 24 months]

    Secondary Outcome Measures

    1. Proportion of participants with carcinoma in situ (CIS) achieving complete response at any time after first dose of PF 07225570 [Baseline up to 24 months]

    2. Durability of complete responses (CRs) as measured from time of documented CR to time of high-grade tumor recurrence, disease progression, or death (whichever occurs first) in participants who achieved a CR [Baseline up to 24 months]

    3. For participants with high-grade Ta/ T1 disease only, Proportion of participants without high-grade-recurrence at each assessment visit. [Baseline up to 24 months]

      Ta is defined as the stage of bladder cancer as a non-invasive papillary carcinoma. T1 is defined as the stage of cancer in which the cancer cells are only growing in the most superficial layer of tissues and have not grown into deeper tissues; in bladder cancer, T1 is defined as an invasion into the lamina propria without invasion into the muscularis propria

    4. Maximum Observed Plasma Concentration (Cmax) of PF-7225570 after a single dose [Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 0.5, 1, 2, 3, 4, 6 and 24 hours after instillation]

    5. Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07225570 after a single dose [Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 0.5, 1, 2, 3, 4, 6 and 24 hours after instillation]

    6. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07225570 after a single dose [Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 0.5, 1, 2, 3, 4, 6 and 24 hours after instillation]

    7. Concentration from maximum to steady state (Cmax,ss) of PF-07225570 after multiple doses [Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 2 hours after instillation]

    8. Time from maximum concentration to steady state (Tmax,ss) of PF-07225570 after multiple doses [Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 2 hours after instillation]

    9. Area under the curve from specified time to steady state (AUCτ,ss) of PF-07225570 after multiple doses [Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 2 hours after instillation]

    10. Urine PF-07225570 concentration after a single dose [Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 0-2 hours, and 4 - 6 hours post-instillation on Cycle 1 Day 1]

    11. Urine PF-07225570 concentration after multiple doses [Pre-dose on Cycle 1 (each cycle is 28 days) Day 1 and at 0-2 hours and 2 - 4 hours post-instillation.]

    12. Progression-Free Survival [Baseline up to 24 months]

    13. Incidence of Radical Cystectomy [Baseline up to 24 months]

    14. Overall survival [Baseline up to 3 years]

    15. Serum sasanlimab concentrations [Pre-dose (within 6 hours) before each administration]

    16. Incidence and titers of neutralizing antibodies (NAb) against sasanlimab [Pre-dose (within 6 hours) before each administration]

    17. Incidence and titers of anti-drug antibodies (ADA) against sasanlimab [Pre-dose (within 6 hours) before each administration]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    Histological confirmed and documented diagnosis of non-muscle invasive urothelial carcinoma

    Participants with recurrent non-muscle invasive bladder cancer (intermediate risk or high risk)

    Ineligible for or elected not to undergo radical cystectomy

    No evidence of upper tract urothelial cancer or cancer within the prostatic urethra as documented by imaging studies performed within 6 months of enrollment

    Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

    Adequate bone marrow, renal and liver function

    Exclusion Criteria:

    Evidence of muscle-invasive, locally advanced or metastatic urothelial carcinoma or concurrent extravesical, non-muscle invasive urothelial carcinoma

    Macroscopic hematuria, traumatic catheterization or active urinary tract infection

    Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent

    Active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) Hepatitis B, Hepatitis C, and known Human Immunodeficiency Virus infection or Acquired Immunodeficiency Syndrome-related illness

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Orlando Health Cancer Institute Orlando Florida United States 32806
    2 Orlando Health Heart Institute (Imaging) Orlando Florida United States 32806
    3 Orlando Health Inc Orlando Florida United States 32806
    4 UF Health Cancer Center at Orlando Health Orlando Florida United States 32806
    5 Columbia University Medical Center - Herbert Irving Pavilion New York New York United States 10032
    6 CUMC Research Pharmacy New York New York United States 10032
    7 MidLantic urology Bala-Cynwyd Pennsylvania United States 19004
    8 Lankenau Medical Center Wynnewood Pennsylvania United States 19096
    9 Seoul National University Bundang Hospital Seongnam-si Kyǒnggi-do Korea, Republic of 13620
    10 Seoul National University Bundang Hospital Seongnam Kyǒnggi-do Korea, Republic of 13620
    11 Seoul National University Hospital Seoul Seoul-teukbyeolsi [seoul] Korea, Republic of 03080
    12 Medical Concierge Centrum Medyczne Warszawa Poland 02-798

    Sponsors and Collaborators

    • Pfizer

    Investigators

    • Study Director: Pfizer CT.gov Call Center, Pfizer

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT05259397
    Other Study ID Numbers:
    • C4661001
    • 2021-005858-28
    First Posted:
    Feb 28, 2022
    Last Update Posted:
    Aug 23, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Pfizer
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 23, 2022